PROJECT SUMMARY This proposal evaluates the pathway between maternal health and infant diarrhea, malnutrition, and death among HIV-exposed, uninfected (HEU) infants. Success among programs designed to prevent mother-to-child transmission of HIV has led to a growing population of HEU children, many of whom experience higher mortality and morbidity than their unexposed peers, primarily from infectious causes. Diarrheal disease is a leading cause of death among children under 5 years old and evidence suggests that HEU children may be more likely to become infected with an enteric pathogen, may be at higher risk of developing diarrhea after infection with such a pathogen, and may be more susceptible to severe disease or death during the ensuing diarrheal episode. Reducing the morbidity and mortality attributed to diarrhea requires a better understanding of the causes and consequences of diarrhea in HEU children, particularly in their first year of life, when diarrhea poses the largest threat to survival and development. While it is well established that poor sanitation and low socioeconomic status are risk factors for diarrhea, the role of maternal health is largely undefined. We wish to understand the relationship between maternal health, infant diarrhea, and malnutrition in this population. We will test the following hypotheses: 1) the incidence of diarrhea among HEU children will be high; maternal health status (CD4 count, viral load, BMI, diarrhea) will be associated with diarrhea incidence independent of family socioeconomic status (maternal education, mother with independent income, number of people per room in house, use of shared toilet); 2) higher diarrhea burden and intensity among HEU infants will be associated with growth faltering and malnutrition independent of family SES (maternal education, mother has independent income, number of people in house, use of shared toilet); and 3) the risk of death in HEU children's first year of life will be associated with diarrhea frequency and persistence independent of family SES (maternal education, mother has independent income, number of people in house, use of shared toilet). These hypotheses will be tested using data from a previously conducted cohort study of nearly 400 HEU infants and their HIV-1 positive mothers in Nairobi, Kenya. We focus on this high risk mother-child dyad because we believe it to be an outcome-enriched population that is likely to be generalizable to other children without HIV exposure. Positive findings would indicate an opportunity to intervene on modifiable factors to decrease diarrhea incidence and consequences.